Just beginning to look into this stock. Been following Anavex for a while.
Cassava vs Anavex - PTI-125 seems to be tau focused. Anavex does miss folded proteins but not specific to FLNA. Are they redundant or could they work together?
Pain Therapeutics to change name to Cassava Sciences and ...
https://www.marketwatch.com › Industries › Pharmaceuticals Mar 27, 2019 - Pain Therapeutics Inc. ptie said Wednesday it's changing its name and ticker to better reflect its focus on developing drugs for neurodegenerative diseases such as Alzheimer's. The company will be named Cassava Sciences Inc. with immediate effect. From March 28, it will start ...
Cassava Sciences Reports Positive Phase 2a Clinical Results in Alzheimer’s Patients GlobeNewswireSeptember 9, 2019, 11:30 AM UTC Lead drug candidate, PTI-125, significantly decreased key biomarkers of neuroinflammation and neurodegeneration in all study patients (p<.001)
Clinical data support initiation of a Phase 2b study in Alzheimer’s in Q3 2019
AUSTIN, Texas, Sept. 09, 2019 (GLOBE NEWSWIRE) -- Cassava Sciences, Inc. (SAVA), a biopharmaceutical company, today reported positive top-line clinical results of its lead drug candidate for Alzheimer’s disease, PTI-125. The Alzheimer’s brain is characterized by a misfolded protein called Filamin A (FLNA); PTI-125 binds to FLNA and restores its normal shape and function. In a Phase 2a study funded by the National Institutes of Health (NIH), treatment with PTI-125 for 28 days significantly reduced biomarkers of Alzheimer’s disease pathology, neuroinflammation and neurodegeneration in patients.
“Based on these encouraging biomarker results, this new treatment could be an important part of the research dialogue in Alzheimer’s disease,” said Dr. Jeffrey Cummings, Research Professor of the Department of Brain Health, UNLV and Director of the Center for Neurodegeneration and Translational Neuroscience of the Cleveland Clinic Lou Ruvo Center for Brain Health. “This drug candidate appears to target some of the more toxic components of the illness. Results will need to be replicated in larger studies to prove it’s a definitive advance in the field.”
The Phase 2a study achieved a 100% responder rate, with all patients responding to PTI-125. A key objective of this first-in-patient study was to measure drug effects on biomarkers in the brain (i.e., in cerebrospinal fluid, or CSF) before and after 28 days of treatment with PTI-125.
Key results include:
Total tau (T-tau) decreased 20% (p<.001)
Phosphorylated tau (P-tau) decreased 34% (p<.0001)
Neurofilament light chain (NfL), a marker for neurodegeneration, decreased 22% (p<.0001)
Neurogranin, a marker for cognitive decline, decreased 32% (p<.0001)
"key biomarkers" used Only 28 days for response, that's only four weeks and I've been saying five. Since it's Tau targeted is it limited to Alzheimer's?
Neurobiol Aging. 2017 Jul;55:99-114. doi: 10.1016/j.neurobiolaging.2017.03.016. Epub 2017 Mar 31. PTI-125 binds and reverses an altered conformation of filamin A to reduce Alzheimer's disease pathogenesis. Wang HY1, Lee KC2, Pei Z2, Khan A3, Bakshi K2, Burns LH4. Author information 1 Department of Physiology, Pharmacology and Neuroscience, City University of New York School of Medicine, New York, NY, USA; Department of Biology and Neuroscience, Graduate school of the City University of New York, New York, NY, USA. Electronic address: hywang@med.cuny.edu. 2 Department of Physiology, Pharmacology and Neuroscience, City University of New York School of Medicine, New York, NY, USA. 3 Department of Physiology, Pharmacology and Neuroscience, City University of New York School of Medicine, New York, NY, USA; Department of Biology and Neuroscience, Graduate school of the City University of New York, New York, NY, USA. 4 Pain Therapeutics, Inc, Austin, TX, USA. Abstract We show that amyloid-ß1-42 (Aß42) triggers a conformational change in the scaffolding protein filamin A (FLNA) to induce FLNA associations with a7-nicotinic acetylcholine receptor (a7nAChR) and toll-like receptor 4 (TLR4). These aberrant associations respectively enable Aß42's toxic signaling via a7nAChR to hyperphosphorylate tau protein, and TLR4 activation to release inflammatory cytokines. PTI-125 is a small molecule that preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its a7nAChR/TLR4 associations and downstream pathologies. Two-month oral PTI-125 administration to triple-transgenic (3xTg) Alzheimer's disease (AD) mice before or after apparent neuropathology and to 8-month wildtypes with milder neuropathologies reduced receptor dysfunctions and improved synaptic plasticity, with some improvements in nesting behavior and spatial and working memory in 3xTg AD mice. PTI-125 also reduced tau hyperphosphorylation, aggregated Aß42 deposition, neurofibrillary tangles, and neuroinflammation. Efficacy in postmortem AD and Aß42-treated age-matched control hippocampal slices was concentration-dependent starting at 1 picomolar (pM) concentration. PTI-125 is the first therapeutic candidate to preferentially bind an altered protein conformation and reverse this proteopathy.
